Search Results (2,424)

Chikungunya virus (CHIKV) is now prevalent in multiple regions worldwide, posing a serious threat to human health. In this study, we have successfully established a rhesus macaque model of Chikungunya virus infection. Notably, while no viral load was detected in liver tissue on day 7 post-infection, significant pathological damage was observed. Single-cell RNA sequencing of liver tissue revealed a reduction in B cells following infection. Among T cells, CD8⁺ T and NKT cells mediated major cytotoxic effects, whereas CD4⁺ T and memory T cells primarily exerted regulatory functions that further enhanced the activation of CD8⁺ T and NKT cells. In macrophages, inflammatory macrophages fc gamma R-mediated phagocytosis upregulated, with multiple key activation-related genes being highly upregulated. Furthermore, we observed that there might be a potential bidirectional activation effect between T cells and macrophages. These results indicate that CHIKV-induced indirect liver injury is likely mediated not only by the virus itself but also, in part, by the activation of hepatic immune cells. Full article

The increasing prevalence of obesity and metabolic disorders poses a major global health challenge. In the present study, purple sweet potato Tainung No. 73 was fermented using Lactobacillus amylovorus OFMLa-73 and Levilactobacillus brevis OFMLb-143 to enrich the specific bioactive metabolite indolelactic acid. Furthermore, supplementation with fermented sweet potato (FSPE) ethanol extract resulted in a significant reduction in body weight gain, adipocyte hypertrophy, and hepatic lipid accumulation, while also improving serum lipid profiles in high-fat diet-induced obesity mice. These physiological improvements were associated with the downregulated expression of adipogenic and inflammatory genes in both liver and adipose tissues. Furthermore, lipidomic analysis revealed that FSPE modulated key lipid species, including ceramides and acylcarnitines, which are implicated in metabolic dysfunction. Collectively, these findings demonstrated that lactic acid fermentation enhanced purple sweet potato’s functional potential, positioning FSPE as a promising candidate for dietary intervention in obesity management. Full article

Background/Objectives: Type 2 diabetes (T2D) and obesity are chronic metabolic disorders associated with cognitive impairment and neuronal damage. The hippocampus, a region sensitive to nutrient excess, is critical for integrating sensory and metabolic signals. This study aimed to determine the early onset of cognitive and motor deficits induced by obesity and/or hyperglycemia and to characterize associated hippocampal alterations in Zucker Diabetic Fatty (ZDF) rats. Methods: Male ZDF rats (13 weeks old) were categorized into three groups: lean control, obese normoglycemic (ZDF-NG), and obese hyperglycemic (ZDF-HG). Assessments included zoometric parameters (weight and adiposity), biochemical assays (glucose tolerance, insulin response, and lipid profile), and behavioral tests (Open Field and Novel Object Recognition). Hippocampal health was evaluated through stereological neuronal density analysis and redox balance markers. Results: Both obese groups exhibited significant visceral adiposity and hyperlipidemia. The ZDF-HG group was further characterized by glucose intolerance, hepatic insulin resistance, and reduced β-cell function. Behavioral results showed that while obesity decreased motor activity, hyperglycemia significantly exacerbated the loss of both short- and long-term recognition memory. Histologically, obesity was associated with decreased neuronal density in the hippocampal DG and CA1 regions. Furthermore, hippocampal ROS was significantly elevated in the ZDF-HG group, and glutathione reductase activity was reduced in both obese phenotypes. Conclusions: The findings demonstrate that obesity initiates hippocampal neurodegeneration and motor decline, and that hyperglycemia severely impairs recognition memory. These results emphasize the critical interplay between metabolic dysfunction and cognitive decline, highlighting the necessity of managing both obesity and T2D to prevent early neurodegenerative changes. Full article

Microcin C7 (McC7) is a ribosomally synthesized antimicrobial peptide that has emerged as a promising candidate due to its dual antibacterial and immunomodulatory activities. This study evaluated the preventive effect of McC7 against cyclophosphamide (CTX)-induced immunosuppression and intestinal injury. An immunosuppression model was established by intraperitoneal CTX injection in mice, which were randomly allocated into five groups (n = 15): a negative control, a CTX model group, and three McC7 treatment groups receiving dietary McC7 at 100, 200, or 400 mg/kg both before and during CTX exposure. Body weight and feed intake were monitored throughout the study. Organ indices, serum biochemical parameters, immune and antioxidant markers, and intestinal morphology were assessed. Splenic T-cell subsets were analyzed by flow cytometry, and gut microbiota composition was evaluated by 16S rRNA sequencing. McC7 supplementation significantly attenuated the CTX-induced reduction in body weight, feed intake, and organ indices, ameliorated markers of hepatic and renal injury, and restored the splenic CD4⁺/CD8⁺ T-cell ratio. McC7 enhanced intestinal mucosal barrier integrity, increased the abundance of beneficial bacteria such as Candidatus Arthromitus and ASF356, and reduced the abundance of the potentially pathogenic genus Bilophila. In conclusion, our results demonstrate that McC7 alleviates CTX-induced immunosuppression by regulating T-cell differentiation, maintaining cytokine homeostasis, and modulating gut microbial composition to support intestinal health. Full article

Background: Malva sylvestris (the common mallow) is an herbaceous species widely used in ethnobotanical practices to treat gastrointestinal, hepatic and urinary inflammation. Objectives: Despite these beneficial effects on human health, the antineoplastic potential of this plant has not yet been fully explored. Thus, in the present study, two human colon cancer cell lines (i.e., HCT-116 and Caco-2) were treated with an extract obtained from M. sylvestris flowers (MFE), whose composition in terms of phytochemicals and microRNAs has been recently published by our research group, to explore its potential bioactivity. Methods/Results: MTT and Trypan blue assays demonstrated that MFE reduced tumour cell growth without causing significant cytotoxicity or apoptosis. Following the diphenylboric acid 2-aminoethyl ester-induced fluorescence of some plant metabolites, microscopy analysis proved that MFE components crossed the cell membranes, accumulating into nuclei. Wound assay and transwell tests documented that MFE was also able to reduce cell motility and invasiveness. In both cell lines qPCR experiments demonstrated that MFE caused the over-expression of factors, like VIMENTIN and E-CADHERIN, which negatively influence epithelial–mesenchymal transition in colon cancers. However, the effects of MFE appeared to be time-, dose- and cell type-dependent. In fact, the treatment induced senescence in P53-null Caco-2 cells (i.e., ROS, β-galactosidase and P21^WAF1/Cip1) and a premise of differentiation (i.e., P27^Kip1) in P53-wild-type HCT-116 cells, also via the CDK2/c-MYC/AKT axis, justifying its antiproliferative property. In parallel, the transfection of tumour cells with pure synthetic miR160b-5p—a microRNA identified in M. sylvestris flowers and predicted to target the human CDK2 transcript—resulted in gene silencing, thereby suggesting its central role in mediating the cross-kingdom effects of MFE on the investigated cancer models. Conclusions: Overall, these findings open new perspectives on the common mallow as a source of potential antimetastatic compounds and on the possible use of its plant microRNAs in the development of gene therapies. Full article

Hepatitis B virus (HBV) infection is a silent epidemic; many infected people are asymptomatic and not aware of the infection. In 2022, it was reported that approximately 254 million people were living with chronic HBV infection globally, majority being in sub-Saharan Africa and Asia. In Kenya, the national HBV prevalence is estimated to be 3.5%. Our study was aimed at identifying key predictors and transmission trends that could inform the development of sustainable prevention models needed to address existing gaps in the national framework towards HBV elimination. We targeted participants seeking health services in Baringo and Kisumu county health facilities and conducted community mass testing in the two counties. Participants were interviewed using a study questionnaire and were tested for hepatitis B surface antigen (HBsAg) using an HBsAg rapid test. Venous blood was collected from participants who tested HBsAg+ for further infection confirmation and linkage to care. Logistic regression was performed to assess factors correlated with HBV infection. Out of 3034 participants, 192 tested positive for HBsAg and the prevalence of HBV infection was 6.3% (95% CI = 0.055–0.072). Intrafamilial infections in Baringo were 15.0%. HBV infection prevalence exceeded 10% among those aged 25–49 years, peaking at 13.1% in the 45–49-year age group and lowest at 1.8% in the 16–19-year age group. Overall, males had a higher prevalence in younger ages, while females above 60 years old were more affected. In multivariable logistic regression, individuals residing in Baringo (aPR = 8.1; 95% CI = 2.2–29.4), users of other injectable drugs (aPR = 6.7; 95% CI = 1.3–204.0), those traditionally circumcised (aPR 1.02; 95% CI = 0.56, 1.88), and staying >5 km from a health care facility (aPR = 10.4; 95% CI = 2.2–49.4) had significantly higher prevalence ratios of being infected with HBV. These different infection predictors underscore the need for different care and prevention approach models. Full article

Diabetes mellitus remains a major global health burden, and many patients do not achieve durable glycemic control despite modern pharmacotherapy. This narrative review synthesizes evidence on plant-derived strategies that may complement standard care, focusing on two clinically aligned domains: glucose-lowering medicinal plants and plant-based sugar substitutes that reduce dietary glycemic load. We summarize key mechanistic pathways, including inhibition of α-amylase/α-glucosidase, reduced intestinal glucose entry and absorption kinetics, glucose-dependent insulinotropic effects, improved insulin signaling, suppression of hepatic gluconeogenesis, and microbiota-linked effects. We critically appraise human evidence for selected botanicals (cinnamon, fenugreek, mulberry, gymnema, gynura, rosehip, and Jerusalem artichoke) and plant sweeteners (stevia and monk fruit). Overall, clinical effects are modest and heterogeneous; the most reproducible signals are observed for mulberry leaf in blunting postprandial glucose excursions, and for cinnamon, fenugreek, and gymnema, where meta-analyses suggest modest improvements in glycemic markers. Stevia and monk fruit are best supported as glycemically neutral sucrose substitutes, while inulin-type fructans show small-to-moderate benefits with sustained intake, limited by gastrointestinal tolerability at higher doses. Key gaps include a shortage of long-term randomized trials using standardized preparations and durable endpoints such as glycated hemoglobin. Plant-derived interventions are therefore best positioned as adjuncts within individualized, evidence-based glycemic management. Full article

Background: Liver fibrosis is a major global public health issue that is only getting worse. The underlying molecular mechanisms of Yindanpinggan Capsule (YDPG), a traditional Chinese medication, are still unknown, although it has shown notable effectiveness in treating fibrosis and other forms of liver injury. Methods: To evaluate the impact of YDPG on liver fibrosis, a mouse model of liver damage caused by carbon tetrachloride (CCL₄) was used. Proteomics, deep learning, network pharmacology, and later biological process validation using Western blot were used to elucidate the possible mechanism of YDPG in reducing liver damage. Results: Following YDPG treatment, we observed a decrease in the fibrosis index and an improvement in liver function. Network pharmacology, deep learning, and proteomics collectively identified the ferroptosis and peroxisome proliferator-activated receptor (PPAR) signaling pathways as pivotal in the anti-fibrosis effects of YDPG on the liver. Further experimental results showed that YDPG inhibited Malondialdehyde (MDA) and Fe²⁺ content and increased Glutathione (GSH) activity in fibrotic liver. Mechanistically, both SLC7A11/GSH pathway-mediated ferroptosis and oxidative stress up-regulated by the PPAR γ/GPx4 pathway were alleviated following YDPG treatment. Conclusions: Our present study corroborates that YDPG limits the progression of liver fibrosis by regulating the PPARγ-GPX4-ferroptosis pathway. These results indicate that YDPG could be a potential medication for hepatic fibrosis. Full article

This study investigated the efficacy of two value-added products derived from silkworm excrement—a concentrated extract (SCE, 20:1) and sodium copper chlorophyllin (SCC)—as functional feed additives for common carp. Diets supplemented with 0.5% SCE, 1.0% SCE, or 0.1% SCC were compared to a basal control. The results revealed a distinct dose-dependent effect for SCE: 0.5% SCE was safe, while 1.0% SCE impaired growth, feed efficiency, and digestive enzyme activity. Both SCE and SCC significantly enhanced lipid metabolism, reducing hepatic lipid deposition and improving serum lipid profiles, albeit through distinct molecular pathways—SCC primarily stimulated catabolism, whereas SCE comprehensively regulated both synthesis and breakdown. Furthermore, SCE demonstrated superior, multi-targeted immunomodulatory capacity by favorably regulating inflammatory cytokine expression, an effect not observed with SCC. Although both additives boosted systemic antioxidant capacity, their specific patterns of enzyme activity and gene expression differed. In conclusion, SCE offers broad-spectrum, synergistic benefits for health modulation, while SCC provides specific, stable bioactivity, highlighting the importance of selecting the appropriate additive form based on desired functional outcomes in aquaculture. Full article

Hepatitis B virus (HBV) remains a major global health threat because covalently closed circular DNA (cccDNA) persists in hepatocytes and limits the efficacy of current antiviral therapies. Effective HBV research and drug screening require culture models that recapitulate the complete viral life cycle and allow for quantitative monitoring of replication. In this study, an 11-amino acid luminescent reporter, HiBiT, was inserted at multiple sites within the preS1 region of a genotype D HBV genome, and the C terminus of preS1 was identified as optimal for maintaining robust replication. We then established HepG2-B4 cells stably replicating HiBiT-HBV with HiBiT at the preS1 C terminus. Extracellular HiBiT activity and supernatant levels of HBV-DNA, HBsAg, and HBcAg increased continuously until day 42 and were reduced by nucleos(t)ide analog treatment, and cccDNA was confirmed by Southern blot analysis. Supernatants from HepG2-B4 cells infected naïve HepG2-NTCP cells and primary human hepatocytes, as shown by extracellular HiBiT activity. Transcriptome analysis revealed distinct gene expression changes in HepG2-B4 cells compared with parental HepG2 cells. These findings indicate that the HepG2-B4 system provides a rapid, quantitative, and scalable platform for HBV replication and infection studies and is suitable for mechanistic investigations and high-throughput antiviral screening. Full article

Cadmium (Cd) is an environmental toxicant that poses significant risks to food safety and public health through its bioaccumulation in the food chain. The liver is a primary target for chronic Cd toxicity, yet the system-level mechanisms, particularly in physiologically relevant swine models, remain incompletely understood. This study employed an integrated multi-omics approach to elucidate the mechanisms of Cd-exposed hepatotoxicity in weaned piglets. We combined histopathological examination, transmission electron microscopy, and transcriptome sequencing. Our results revealed severe hepatic damage, characterized by disorganized architecture, vacuolar degeneration, mitochondrial dysfunction, and autophagic activation. Network toxicology predicted 3727 potential targets of Cd-exposed liver injury, while transcriptomics identified 1092 differentially expressed genes (DEGs). Crucially, the convergent analysis of both datasets demonstrated that the PI3K-Akt signaling pathway was the central hub, pinpointing it as a pivotal mechanism in Cd-driven hepatotoxicity. Functional enrichment analyses further highlighted dysregulation in immune-inflammatory responses, lipid metabolism, and oxidative stress. Our findings provide a comprehensive systems-level perspective on chronic Cd hepatotoxicity in a translational swine model. We propose the PI3K-Akt pathway and other identified core targets (EGFR, histones, ribosomal proteins) as critical biomarkers for monitoring Cd contamination in swine production chains, offering valuable insights for environmental risk assessment and agricultural product safety. Full article

Background and Aims: Changes in hepatitis delta virus (HDV) epidemiology have been highlighted recently in the context of increasing worldwide migrations. The lack of comprehensive real-world data on HDV in the Valencia region highlights the need for a structured registry to accurately estimate disease prevalence and burden and to generate robust real-world evidence on clinical outcomes and therapeutic effectiveness. We aimed to better understand the barriers for successful HDV patient care in our region by establishing a registry as well as linking previously under-recognized or lost to follow-up (FU)cases to care. Methods: After a search of all possible HDV cases in a Spanish region, attempts were made (through letters and phone calls) to relink to care those lost to FU. Two approaches were undertaken: (i) search of the Microbiology Labs Database, and (ii) clinical chart review from adult patients attending the Hepatology or Infectious Disease (ID) Units outpatient clinics of the three participant hospitals between January 2011 and June 2021. Results: Only one third of anti-HDV positive patients without adequate clinical management could be successfully linked or re-linked to care, highlighting a substantial gap in follow-up. Among 243 HDV cases detected (7.5% of HBsAg-positive patients), 111 belonged to the hospitals’ health department, and after excluding deceased or transplanted individuals, the final study cohort consisted of 84 patients. Of these, 27.4% were adequately followed in Hepatology or Infectious Disease Clinics, 11.9% had been inadequately followed recently, 45.2% had been lost to follow-up for several years, and 15.5% had never been evaluated in outpatient clinics. Overall, only a third of the patients without adequate clinical management could be successfully linked/relinked to care. Conclusions: In our setting, only a minority of anti-HDV positive patients are adequately managed in specialized outpatient clinics, with unsuccessful attempts to link many patients to care, particularly among young migrant men. These findings underscore the need for alternative strategies, such as decentralized testing, reflex testing, and the involvement of patient navigators or social workers, to strengthen linkage to care and improve retention. Full article

Curcumin, the major polyphenolic constituent of Curcuma longa, has been widely investigated as a hepatoprotective adjunct due to its antioxidant and immunomodulatory properties. This review evaluates the relevance of curcumin for the prevention and management of liver dysfunction and hepatitis in pigs by synthesizing available porcine evidence and integrating mechanistic insights from translational liver injury models where pig-specific data remain limited. Across experimental hepatic injury contexts, curcumin administration is most consistently associated with reduced biochemical and structural indicators of hepatocellular damage, including decreased aminotransferase activity, attenuation of lipid peroxidation, and enhancement of endogenous antioxidant defenses. These effects are mechanistically linked to suppression of pro-inflammatory signaling pathways, particularly NF-κB-related transcriptional activity and inflammasome-associated responses, together with reduced expression of key cytokines such as TNF-α, IL-1β, and IL-6. Concurrent activation of Nrf2-centered cytoprotective pathways and induction of phase II antioxidant enzymes (including HO-1, GST, and NQO1) appear to constitute a conserved axis supporting hepatic oxidative stress resilience. In swine-relevant infectious settings, available data further support antiviral activity against selected porcine pathogens, including classical swine fever virus and porcine reproductive and respiratory syndrome virus, potentially mediated through interference with lipid-dependent stages of viral replication and modulation of Kupffer cell activation. Although combination strategies with established hepatoprotective approaches are conceptually attractive, current synergy evidence remains heterogeneous and largely extrapolated. Overall, curcumin represents a plausible adjunct candidate for supporting porcine liver health; however, translation into practice will depend on resolving formulation-dependent bioavailability constraints and strengthening the pig-specific evidence base. Full article

This study aimed to evaluate the effects of trimethylamine oxide (TMAO) supplementation (0.5% and 1%) to a high-carbohydrate diet on the growth performance, liver health, hepatic metabolome, intestinal microbiota and disease resistance of largemouth bass (Micropterus salmoides). After an eight-week feeding trial with three replicates, fish fed with TMAO-supplemented diets showed growth-promoting potential with increased difference with a prolonged rearing period. Importantly, TMAO supplementation significantly improved liver structure and function, with reduced intrahepatic glycogen accumulation due to reprogrammed glycogen metabolism, including down-regulated gys2 and ugp2b but up-regulated pygl expression levels. Targeted liver metabolomics analysis indicated the enhanced synthesis of long-chain fatty acid and amino acid in the 1% TMAO group, accompanied by decreased cortisol, indicating the attenuation of the stress response. Furthermore, TMAO supplementation changed the structure of the intestinal microbiota and particularly the intestinal content of Romboutsia, an important probiotic that can effectively utilize different kinds of dietary carbohydrate, showed an increasing trend with the increased TMAO supplementation levels. Finally, after sampling, all remaining fish were challenged with Nocardia seriolae. TMAO supplementation significantly enhanced the immune clearance function of largemouth bass against invading N. seriolae, with alleviated granulomatous nodules within liver but enhanced hepatic expression levels of nlrp3, caspase1, il-1β and il-18. These results collectively underscore the finding that TMAO may promote intestinal Romboutsia growth and reprogram hepatic metabolism to improve liver health, giving TMAO potential as a feed additive for growth and health promotion in largemouth bass. Full article

Metabolic associated fatty liver disease (MAFLD), redefined from non-alcoholic fatty liver disease (NAFLD), is a global health concern driving the search for dietary interventions based on natural compounds. Phloroglucinaldehyde (PGA), a primary phenolic metabolite of the widely consumed anthocyanin cyanidin-3-glucoside (C3G) found in berries and other fruits, has emerged as a promising candidate due to its potential higher bioavailability than its parent compound. This study investigates the protective effects of PGA against high-fat diet (HFD)-induced MAFLD. Using both in vitro (LO2 cells) and in vivo (C57BL/6J mice) models, we found that PGA administration significantly attenuated body weight gain and hepatic steatosis, while reducing serum levels of TG, TC, liver transaminases (AST & ALT), and insulin resistance (p < 0.05). Further liver lipidomic profiling revealed that PGA supplementation specifically down-regulated 46 lipid species (p < 0.05), predominantly triglycerides characterized by long-chain and very-long-chain saturated fatty acids. Mechanistically, PGA enhanced the hepatic antioxidant capacity by increasing superoxide dismutase (SOD) activity (p < 0.05) and decreasing malondialdehyde (MDA) (p < 0.05) and exerted anti-inflammatory effects by reducing pro-inflammatory cytokines (IL-6, TNF, MCP-1) (p < 0.05) and endotoxin levels (p < 0.05). Correlation analyses further linked the down-regulated lipids to improvements in oxidative stress and inflammation. Our findings underscore that PGA, a key bioactive metabolite derived from dietary anthocyanins, alleviates MAFLD through its potent antioxidant and anti-inflammatory properties, highlighting its potential as a functional food ingredient or nutraceutical for metabolic health. Full article